Category: Nevin Manimala

JMIR Form Res. 2023 Jan 18. doi: 10.2196/39994. Online ahead of print.

ABSTRACT

BACKGROUND: Older adults are particularly at risk from infectious diseases, including serve complications, hospitalization, and death.

OBJECTIVE: This study aimed to explore the drivers of vaccine hesitancy among older adults based on the 3Cs framework, where socioeconomic status and vaccination history played as roles of moderators.

METHODS: A cross-sectional questionnaire survey was conducted in Jiangsu Province, China between June 1, 2021, and July 20, 2021. Older adults (above 60 years) were recruited using a stratified sampling method. Vaccine hesitancy was setting influenced by confidence, complacency, and convenience in the model. Socioeconomic status and vaccination history processed through the item parceling method were used to moderate associations between the 3Cs and hesitancy. Hierarchical regression analyses and structural equation modeling were used to test the validity of the new framework. We performed 5000 trials of bootstrapping to calculate the 95% confidence interval (CI) of the pathway’s coefficients.

RESULTS: A total of 1341 older adults (response rate: 87%) participated. The age was 71.3 ± 5.4 years old and 44.7% of participants were men. Confidence [b = 0.967, 95% CI: 0.759, 1.201, P = .002], convenience (b = 0.458, 95% CI: 0.333, 0.590, P = .002), and less complacency (b = 0.301, 95% CI: 0.187, 0.408, P = .002) were positively associated with less vaccine hesitancy. Socioeconomic status weakened the positive effect of low complacency (b = -0.065, P = .03) on low vaccine hesitancy. Coronavirus disease 2019 (COVID-19) vaccination history negatively moderated the positive association between confidence (b = -0.071, P = .02) and lower vaccine hesitancy.

CONCLUSIONS: Our study identified that confidence was the more influential dimension in reducing vaccine hesitancy among older adults. COVID-19 vaccination history, as well as confidence, have a positive association with less vaccine hesitancy, and it could weaken the role of confidence in vaccine hesitancy. Socioeconomic status had a substitution relationship with less complacency, which suggested a competitive positive association between them on less vaccine hesitancy.

PMID:36693149 | DOI:10.2196/39994

Ear Hear. 2023 Jan 25. doi: 10.1097/AUD.0000000000001338. Online ahead of print.

ABSTRACT

OBJECTIVES: Systemic steroids are the most common first-line therapy in sudden sensorineural hearing loss (SSNHL), with significant improvement in hearing outcomes in over 60% of patients. It is unknown why 40% of patients do not respond to systemic steroid therapy. Salvage treatment includes intratympanic steroids (ITS) and hyperbaric oxygenation (HBO) therapy, with inconsistent results reported. This study aimed to compare the results of ITS and HBO therapy in patients with SSNHL that previously failed systemic steroid therapy.

DESIGN: This is a comparative retrospective nonrandomized interventional cohort study, enrolling 126 patients with SSNHL. Out of these, 35 patients received HBO therapy, 43 patients received ITS, and 48 patients did not receive any second-line therapy (control group). Pure-tone audiograms were performed before and after the salvage therapy in the IT and HBO groups and at the same time interval in the control group. Study variables included age, time until therapy initiation, tinnitus status, and hearing outcomes, with a cutoff criteria of cumulative >30 dB improvement on all frequencies indicating recovery.

RESULTS: ITS and HBO therapy were associated with statistically significant hearing recovery at all frequencies compared to systemic steroids. The results show an average hearing improvement of 13.6 dB overall frequencies (250 to 8000 Hz) after ITS therapy and 7.4 dB in HBO therapy in comparison to the control group. Presence of significant hearing improvement positively correlated with age, ITS therapy, and HBO therapy. Presence of tinnitus before therapy was negatively correlated with hearing improvement. Patients with tinnitus present at the start of therapy improve 4.67 dB less on average compared to those without tinnitus. ITS therapy significantly reduced tinnitus compared to the other two treatment options. Patients with tinnitus present before therapy significantly improve hearing at low frequencies, compared to the control group.

CONCLUSIONS: ITS and HBO therapy show superior hearing results compared to observation alone after failed oral steroid therapy for SSNHL. ITS shows an additional positive impact on tinnitus reduction and shows superior hearing outcomes after salvage therapy.

PMID:36693145 | DOI:10.1097/AUD.0000000000001338

PLoS One. 2023 Jan 24;18(1):e0266637. doi: 10.1371/journal.pone.0266637. eCollection 2023.

ABSTRACT

BACKGROUND: Chronic non-communicable disease comorbidities are a major problem faced by people living with HIV (PLHIV). Obesity is an important factor contributing to such comorbidities and PLHIV face an elevated risk of obesity. However, there is data paucity on the intersection of obesity and HIV in adolescents and youth living with HIV (AYLHIV) in sub-Saharan Africa. We therefore aimed to investigate the prevalence of abdominal obesity and associated multilevel factors in AYLHIV in peri-urban Cape Town, South Africa.

METHODS: We conducted a cross-sectional study enrolling AYLHIV aged 15-24 years attending primary healthcare facilities in peri-urban Cape Town in 2019. All measures, except for physical examination measures, were obtained via self-report using a self-administered electronic form. Our outcome of interest was abdominal obesity (waist-to-height ratio ≥ 0.5). We collected individual-level data and data on community, built and food environment factors. Data was summarized using descriptive statistics, stratified by obesity status. Multilevel logistic regression was conducted to investigate factors associated with abdominal obesity, adjusted for sex and age.

FINDINGS: A total of 87 participants were interviewed, 76% were female and the median age was 20.7 (IQR 18.9-23.0) years. More than two fifths had abdominal obesity (41%; 95% CI: 31.0-51.7%), compared to published rates for young people in the general population (13.7-22.1%). In multilevel models, skipping breakfast (aOR = 5.42; 95% CI: 1.32-22.25) was associated with higher odds of abdominal obesity, while daily wholegrain consumption (aOR = 0.20; 95% CI: 0.05-0.71) and weekly physical activity (aOR = 0.24; 95% CI: 0.06-0.92) were associated with lower odds of abdominal obesity. Higher anticipated stigma was associated with reduced odds of obesity (aOR = 0.58; 95% CI: 0.33-1.00). Land-use mix diversity (aOR = 0.52; 95% CI: 0.27-0.97), access to recreational places (aOR = 0.37; 95% CI: 0.18-0.74), higher perceived pedestrian and traffic safety (aOR = 0.20; 95% CI: 0.05-0.80) and having a non-fast-food restaurant within walking distance (aOR = 0.30; 95% CI: 0.10-0.93) were associated with reduced odds of abdominal obesity. The main limitations of the study were low statistical power and possible reporting bias from self-report measures.

CONCLUSIONS: Our findings demonstrate a high prevalence of abdominal obesity and highlight multilevel correlates of obesity in AYLHIV in South Africa. An intersectoral approach to obesity prevention, intervening at multiple levels is necessary to intervene at this critical life stage.

PMID:36693111 | DOI:10.1371/journal.pone.0266637

Proc Natl Acad Sci U S A. 2023 Jan 31;120(5):e2212755120. doi: 10.1073/pnas.2212755120. Epub 2023 Jan 24.

ABSTRACT

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. The current treatment regime is long and expensive, and missed doses contribute to drug resistance. Therefore, development of new anti-TB drugs remains one of the highest public health priorities. Mtb has evolved a complex cell envelope that represents a formidable barrier to antibiotics. The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. However, the role of PIMs in the structure and function of the membrane remains elusive. Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. To further validate the model, we tested known anti-TB drugs and demonstrated that our models agree with experimental results. Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function.

PMID:36693100 | DOI:10.1073/pnas.2212755120

PLoS One. 2023 Jan 24;18(1):e0280906. doi: 10.1371/journal.pone.0280906. eCollection 2023.

ABSTRACT

BACKGROUND: Hereditary hypothyroidism represents a concern for dog breeders; thus, surveillance programs have been established for several dog breeds.

METHODS: Thyroid profiles (total thyroxine (TT4), thyrotropin (thyroid stimulating hormone (TSH)), and thyroglobulin autoantibodies (TgAA)) collected as part of a breed surveillance program in Eurasians (2009-2017) were retrospectively analyzed. The study included data from 1,501 Eurasians from a German breeding club. Classification was exclusively based on laboratory data. Hypothyroidism was defined as a combined decrease in TT4 and increase in TSH in serum and was classified as TgAA-positive and TgAA-negative hypothyroidism. Thyroglobulin autoantibodies (TgAA) independent of the concentrations of TT4 and TSH were determined. The overall prevalence of hypothyroidism, TgAA-positive hypothyroidism, TgAA-negative hypothyroidism and TgAA-positivity was assessed when the dogs entered the program. Follow-up laboratory data was available for 324 dogs without hypothyroidism on initial examination.

RESULTS: The initial screening was performed at a median age of 18 months (interquartile range (IQR): 15-29). The overall prevalence of hypothyroidism was 3.9% (n = 58; 95% CI: 2.9-4.8%) and the prevalence of a positive TgAA status was 7.9% (n = 118; 95% CI: 6.6-9.3%). The prevalence of TgAA-positive and TgAA-negative hypothyroidism was 1.7% (n = 26; 95% CI: 1.1-2.4%) and 2.1% (n = 32; 95% CI: 1.4-2.9%), respectively. 22.0% of dogs with positive TgAA status (26/118) were already hypothyroid on initial examination. Overall, 42.5% (17/40) of TgAA-positive dogs on initial examination developed hypothyroidism on follow-up.

CONCLUSION: The results of this study demonstrate that the Eurasian dog breed exhibits a relevant risk for hypothyroidism and presence of TgAA. The predictive value of TgAA for hypothyroidism or developing hypothyroidism was high in this breed. Further investigations with longitudinal studies in individual dogs are warranted.

PMID:36693083 | DOI:10.1371/journal.pone.0280906

PLoS One. 2023 Jan 24;18(1):e0280990. doi: 10.1371/journal.pone.0280990. eCollection 2023.

ABSTRACT

BACKGROUND: The World Health Organization declared a pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on March 11, 2020. The standardized approach of disability-adjusted life years (DALYs) allows for quantifying the combined impact of morbidity and mortality of diseases and injuries. The main objective of this study was to estimate the direct impact of COVID-19 in France in 2020, using DALYs to combine the population health impact of infection fatalities, acute symptomatic infections and their post-acute consequences, in 28 days (baseline) up to 140 days, following the initial infection.

METHODS: National mortality, COVID-19 screening, and hospital admission data were used to calculate DALYs based on the European Burden of Disease Network consensus disease model. Scenario analyses were performed by varying the number of symptomatic cases and duration of symptoms up to a maximum of 140 days, defining COVID-19 deaths using the underlying, and associated, cause of death.

RESULTS: In 2020, the estimated DALYs due to COVID-19 in France were 990 710 (1472 per 100 000), with 99% of burden due to mortality (982 531 years of life lost, YLL) and 1% due to morbidity (8179 years lived with disability, YLD), following the initial infection. The contribution of YLD reached 375%, assuming the duration of 140 days of post-acute consequences of COVID-19. Post-acute consequences contributed to 49% of the total morbidity burden. The contribution of YLD due to acute symptomatic infections among people younger than 70 years was higher (67%) than among people aged 70 years and above (33%). YLL among people aged 70 years and above, contributed to 74% of the total YLL.

CONCLUSIONS: COVID-19 had a substantial impact on population health in France in 2020. The majority of population health loss was due to mortality. Men had higher population health loss due to COVID-19 than women. Post-acute consequences of COVID-19 had a large contribution to the YLD component of the disease burden, even when we assume the shortest duration of 28 days, long COVID burden is large. Further research is recommended to assess the impact of health inequalities associated with these estimates.

PMID:36693071 | DOI:10.1371/journal.pone.0280990

PLoS One. 2023 Jan 24;18(1):e0280936. doi: 10.1371/journal.pone.0280936. eCollection 2023.

ABSTRACT

Several studies have demonstrated the de novo formation of lymphatic vessels or the reorganization of lymphatic sinus in tumor-draining lymph nodes, partly preceding the detection of lymphatic metastases. This “lymphovascular niche”is supposed to facilitate the survival of metastatic tumor cells. Few studies on nodal lymphangiogenesis in invasive breast cancer (BC) have been published, not considering tumor-free sentinel lymph nodes (SLN) and tumor types. Specimens of SLN and/ or non-SLN (NSLN) of 95 patients with BC were examined immunohistochemically for expression of the lymphatic endothelial marker D2-40 (podoplanin) on lymphatic vessels and the subcapsular sinus. The number of D2-40-positive lymph vessels in metastases was evaluated with two morphometric methods (Chalkley count and number per HPF). Data was explored with respect to TNM parameters, grading, tumor type, size of metastasis, lymph vessel number and hormone receptor/HER2 status with appropriate statistical tests. Lymphangiogenesis was detected exclusively in and around BC metastases with both methods for lymph vessel quantification being equivalent. Lymph vessel number correlated with the size of metastases, being significantly higher in larger metastases (p < 0.001). There was no significant statistical difference with respect to tumor types. Intranodal lymphangiogenesis could not be verified by D2-40 staining in any of the tumor-free lymph nodes examined. However, D2-40 was frequently detected in sinus endothelial/virgultar cells of the subcapsular sinus, partly with strong uniform positivity. Staining intensity and stained proportion of the subcapsular sinus were markedly heterogeneous, significantly correlating with each other both in SLN and NSLN (p < 0.001). A higher proportion of D2-40 stained subcapsular sinus in SLN was significantly associated with worse overall survival (p = 0.0036) and an independent prognostic parameter in multivariate analysis (p = 0.033, HR 2.87). Further studies are necessary to elucidate the biological and clinical significance of the observed immunophenotypic variations of nodal sinus endothelium.

PMID:36693068 | DOI:10.1371/journal.pone.0280936

PLoS One. 2023 Jan 24;18(1):e0280827. doi: 10.1371/journal.pone.0280827. eCollection 2023.

ABSTRACT

In large areas of the ocean, iron concentrations are insufficient to promote phytoplankton growth. Numerous studies have been conducted to characterize the effect of iron on algae and how algae cope with fluctuating iron concentrations. Fertilization experiments in low-iron areas resulted primarily in diatom-dominated algal blooms, leading to laboratory studies on diatoms comparing low- and high-iron conditions. Here, we focus on the short-term temporal response following iron addition to an iron-starved open ocean diatom, Thalassiosira oceanica. We employed the NanoString platform and analyzed a high-resolution time series on 54 transcripts encoding proteins involved in photosynthesis, N-linked glycosylation, iron transport, as well as transcription factors. Nine transcripts were iron-responsive, with an immediate response to the addition of iron. The fastest response observed was the decrease in transcript levels of proteins involved in iron uptake, followed by an increase in transcript levels of iron-containing enzymes and a simultaneous decrease in the transcript levels of their iron-free replacement enzymes. The transcription inhibitor actinomycin D was used to understand the underlying mechanisms of the decrease of the iron-responsive transcripts and to determine their half-lives. Here, Mn-superoxide dismutase (Mn-SOD), plastocyanin (PETE), ferredoxin (PETF) and cellular repressor of EA1-stimulated genes (CREGx2) revealed longer than average half-lives. Four iron-responsive transcripts showed statistically significant differences in their decay rates between the iron-recovery samples and the actD treatment. These differences suggest regulatory mechanisms influencing gene transcription and mRNA stability. Overall, our study contributes towards a detailed understanding of diatom cell biology in the context of iron fertilization response and provides important observations to assess oceanic diatom responses following sudden changes in iron concentrations.

PMID:36693065 | DOI:10.1371/journal.pone.0280827

PLoS One. 2023 Jan 24;18(1):e0279779. doi: 10.1371/journal.pone.0279779. eCollection 2023.

ABSTRACT

BACKGROUND: Despite the worldwide campaigns of COVID-19 vaccinations, the pandemic is still a major medical and social problem. The Ortho VITROS SARS-CoV-2 spike-specific quantitative IgG (VITROS S-IgG) assay has been developed to assess neutralizing antibody (NT antibody) against SARS-CoV-2 spike (S) antibodies. However, it has not been evaluated in Japan, where the total cases and death toll are lower than the rest of the world.

METHODS: The clinical performance of VITROS S-IgG was evaluated by comparing with the NT antibody levels measured by the surrogate virus neutralizing antibody test (sVNT). A total of 332 serum samples from 188 individuals were used. Of these, 219 samples were from 75 COVID-19 patients: 96 samples from 20 severe/critical cases (Group S), and 123 samples from 55 mild/moderate cases (Group M). The remaining 113 samples were from 113 healthcare workers who had received 2 doses of the BNT162b2 vaccine.

RESULTS: VITROS S-IgG showed good correlation with the cPass sVNT assay (Spearman rho = 0.91). Both VITROS S-IgG and cPass sVNT showed significantly higher plateau levels of antibodies in Group S compared to Group M. Regarding the humoral immune responses after BNT162b2 vaccination, individuals who were negative for SARS-CoV-2 nucleocapsid (N)-specific antibodies had statistically lower titers of both S-IgG and sVNT compared to individuals with a history of COVID-19 and individuals who were positive for N-specific antibodies without history of COVID-19. In individuals who were positive for N-specific antibodies, S-IgG and sVNT titers were similar to individuals with a history of COVID-19.

CONCLUSIONS: Although the automated quantitative immunoassay VITROS S-IgG showed a reasonable correlation with sVNT antibodies, there is some discrepancy between Vitros S-IgG and cPass sVNT in milder cases. Thus, VITROS S-IgG can be a useful diagnostic tool in assessing the immune responses to vaccination and herd immunity. However, careful analysis is necessary to interpret the results.

PMID:36693058 | DOI:10.1371/journal.pone.0279779

PLoS One. 2023 Jan 24;18(1):e0280957. doi: 10.1371/journal.pone.0280957. eCollection 2023.

ABSTRACT

PURPOSE: To determine the amounts of time spent in physical activity (PA), sedentary behaviour (SB), and sleep in the Thai population, as well as their sociodemographic correlates and changes over time.

METHODS: We analysed cross-sectional data collected in a population-representative, stratified random sample of 135,824 Thais aged 10 years and over as part of the two most recent Thai National time-use surveys (2009 and 2015). Daily activities reported by the participants were coded using the International Classification of Activities for Time-Use Statistics (ICATUS) and categorised as PA, SB, or sleep.

RESULTS: In the latest survey, participants spent on average the largest amount of time sleeping (geometric mean [g] = 9.44 h/day; 95% confidence interval [CI]: 9.42, 9.47), followed by PA (g = 8.60 h/day; 95% CI: 8.55, 8.64) and SB (g = 5.96 h/day; 95% CI: 5.93, 6.00). The time spent in PA was higher on weekdays, while the amounts of SB and sleep were higher on weekends (p < 0.05). Males, older age groups, and unemployed people spent less time in PA and more time in SB, compared with other population groups (p < 0.05). We found a relatively large increase in SB (mean difference [d] = 39.64 min/day; 95% CI: 36.18, 42.98) and decrease in PA (d = 54.33 min/day; 95% CI: -58.88, -49.30) over time. These findings were consistent across most sociodemographic groups, with the most concerning shifts from active to sedentary lifestyle found among people with a higher education degree and on weekends.

CONCLUSIONS: Our findings revealed a shift to a more sedentary lifestyle in the Thai population. Public health interventions should focus on improving time use among males, older age groups, and unemployed people, while preventing the rapid decrease in PA and increase in SB among those with a higher education degree and on weekends.

PMID:36693050 | DOI:10.1371/journal.pone.0280957